The goals of this research are: 1) a detailed understanding of the structure and function of the thyroglobulin molecule; and 2) an understanding of the process of thyroxine biosynthesis and those factors which regulate it. The research proposed here continues a study to identify those regions of the thyroglobulin molecule which are iodinated by thyroid peroxidase and serve to form thyroxine. The amino acid sequence of several of the small polypeptides seen in the thyroglobulin structure, along with the amino acid sequence of a tryptic peptide which contains large amounts of iodine in the form of iodinated amino acids, will be studied. The proteolytic activities of thyroid tissue will be studied. Fluorescence polarization spectroscopy will be used to examine the hydrodynamic behavior of thyroid stimulating hormone under various conditions and at very low concentrations. The interaction of thyroid stimulating hormone with thyroid microsomes, lymphocytes and serum proteins will be examined in order to help define the molecular mechanism of the thyrotropin stimulation of thyroid tissues.